Abstract
The effects of three hydrophilic polymers, namely, carboxymethyl cellulose sodium (CMC-Na), polyvinyl alcohol (PVA) and poloxamer-188 (PXM-188) on the solubility and dissolution of diflunisal (DIF) in complexation with β-cyclodextrin (βCD) or hydroxypropyl β-cyclodextrin (HPβCD), were investigated. The kneading method was used at different drug to cyclodextrin weight ratios. Increases in solubility and drug release were observed with the DIF/βCD and DIF/HPβCD complexes. The addition of hydrophilic polymers at 2.5, 5.0 and 10.0% w/w markedly improved the complexation and solubilizing efficiency of βCD and HPβCD. Fourier-transform infrared (FTIR) showed that DIF was successfully included into the cyclodextrin cavity. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) confirmed stronger drug amorphization and entrapment in the molecular cage of cyclodextrins. The addition of PVA, CMC-Na or PXM-188 reduced further the intensity of the DIF endothermic peak. Most of the sharp and intense peaks of DIF disappeared with the addition of hydrophilic polymers. In conclusion, PXM-188 at a weight ratio of 10.0% w/w was the best candidate in enhancing the solubility, stability and release of DIF.
Highlights
The major challenges of BCS class II drugs are poor aqueous solubility and dissolution [1,2,3,4]
Diflunisal was supplied by AK Scientific (Union city, San Francisco, USA)
All other materials were of analytical reagent grade and used as received
Summary
The major challenges of BCS class II (low solubility and high permeability) drugs are poor aqueous solubility and dissolution [1,2,3,4]. Various techniques have been introduced to overcome the limitation of BCS Class II drugs, which include salt formation, lipid-based formulations, particle size reduction, solid dispersions and complexation with cyclodextrins or its derivatives [5,6,7,8,9]. Complexation of poorly soluble drugs with cyclodextrins has become one of the important approaches in formulation development [10,11,12]. The whole molecule appears as a cone/torus shape due to limited rotation of bonds connecting the glucopyranose units, providing the opportunity to lodge a variety of suitably sized lipophilic drugs within the cavity [13]. Favorable modifications to the physicochemical properties of poorly soluble drugs, namely, solubility, stability, dissolution rate and bioavailability, could be achieved via complexation with cyclodextrins [14]. It is considered a new salicylic acid synthetic analog, in which the difluorophenyl group (at the C5 position of salicylic acid) is responsible for imparting lipophilic character to the molecule [17]
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